The primary aim of this double-blind, randomized, placebo-controlled Phase 1a/b study was to assess the safety and pharmacokinetics of KL1333, Abliva’s candidate drug for chronic oral treatment of PMD, both in healthy volunteers and in patients. Data from the study confirms single ascending dose (SAD) data from a prior Phase 1 study, and showed, for the first time, multiple-ascending dose (MAD) data from healthy volunteers and multiple day dosing in patients. The study included an analysis on the food effect and split dosing of KL1333 in healthy volunteers as well as a full characterization of pharmacokinetic parameters in both healthy volunteers and patients with primary mitochondrial diseases.

“This is a seminal trial for people with primary mitochondrial diseases. The study findings support progression of an innovative therapeutic agent into the later stages of drug development in a patient population with high unmet medical needs. I look forward to an ongoing partnership with Abliva as they advance their portfolio of novel drug candidates towards regulatory approval,” said Dr. Robert Pitceathly, Chief Investigator of Part 1b of the study, MRC Clinician Scientist and Honorary Consultant Neurologist at University College London Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery.

In a cohort of eight patients with primary mitochondrial diseases (six dosed with KL1333, two with placebo), there were signs of efficacy across well-established, relevant clinical endpoints including two different patient-reported fatigue endpoints and a functional endpoint, 30-Second Sit to Stand. Although the study was not primarily designed to evaluate efficacy and the duration of dosing was only 10 days, the mean of change was numerically greater in the patients dosed with KL1333 compared to the placebo group for all three endpoints. In addition, there was an association between levels of KL1333 in the patients and efficacy.

“We were pleased to see the movement of two independent fatigue scales after only 10 days of dosing as it suggests that KL1333, through its mechanism of action, works quickly and it gives us increasing confidence in the use of fatigue as a primary endpoint in our upcoming clinical study. The fact that the patients with the highest exposure of KL1333 had the best effects, with clinically meaningful improvements across all three endpoints, strengthens our clinical program moving into our Phase 2/3 study,” said Magnus Hansson, Abliva’s CMO.

As Abliva previously communicated, there were no serious adverse events in the study. Further review of the safety data confirms no safety signals and reinforces the strong safety profile of KL1333 after dosing over 100 healthy volunteers and patients throughout development. KL1333 was generally well tolerated across patients and healthy volunteers with the main dose-limiting tolerability of gastrointestinal side effects, an effect that was improved by administering the drug two or three times per day.

Additionally, a second pharmacology study, one evaluating the interaction of KL1333 with seven enzymes (CYPs) that metabolize other drugs, has just completed. In the study there was only mild inhibition of one of the less common enzymes (CYP1A2) across the cohort, further strengthening the program as it moves forward in development.

“This data package increases our confidence in our upcoming Phase 2/3 study as we have confirmed the safety of KL1333, seen early signals of efficacy from relevant clinical outcomes, and identified a good dosing regime”, said Ellen Donnelly, Abliva’s CEO. “The company will now review the totality of the data and work to finalize our clinical protocol as we move towards IND submission later this year.”